Full Papers
Candidate pharmacogenetic signals at CCL2 and ITPA associated with JAK inhibitor response in Taiwanese rheumatoid arthritis
T.-Y. Hsieh1, I.-C. Chen2, T.-S. Wu3, S.-M. Lo4, C.-M. Kao5, Y.-J. Chen6, W.-N. Huang7, F.-C. Liu8, Y.-M. Chen9
- Department of Medical Education, Taichung Veterans General Hospital, Taichung; and Faculty of Medicine, National Defense Medical Center, Taipei, Taiwan.
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan.
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
- Department of Medical Research, Taichung Veterans General Hospital, Taichung; and Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
- Department of Medical Research, Taichung Veterans General Hospital, Taichung; Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung; and Faculty of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan.
- Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung; Faculty of Medicine, National Yang-Ming Chiao Tung University, Taipei; and Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
- Rheumatology/Immunology and Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
- Department of Medical Research, Taichung Veterans General Hospital, Taichung; Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung; Faculty of Medicine, National Yang-Ming Chiao Tung University, Taipei; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung; Graduate Institute of Clinical Medicine, College of Medicine, National Chung Hsing University, Taichung; and Precision Medicine Research Center, College of Medicine, National Chung Hsing University, Taichung, Taiwan. ymchen1@vghtc.gov.tw
CER19362
Full Papers
PMID: 41841677 [PubMed]
Received: 27/09/2025
Accepted : 23/02/2026
In Press: 12/03/2026
Abstract
OBJECTIVES:
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by persistent synovial inflammation. Janus kinase inhibitors (JAKi) are effective targeted therapies for RA, yet clinical responses vary. We aimed to identify genetic predictors of JAKi effectiveness in Taiwanese patients with RA.
METHODS:
In this retrospective study, 275 RA patients treated with tofacitinib, baricitinib, or upadacitinib in the Taiwan Precision Medicine Initiative (TPMI) were recruited and classified as Effective or Non-effective. Fifty-eight candidate single-nucleotide polymorphisms (SNPs) were evaluated using existing Taiwan Biobank v2 array data. We integrated cell-type-specific eQTL resources (scQTLbase) and single-cell RNA sequencing (scRNA-seq) to support gene-level associations.
RESULTS:
In this cohort (Effective, n=217; Non-effective, n=58), CCL2 rs1024611/rs4586 and ITPA rs1127354 were the top nominal candidates (all p<0.05). In scQTLbase (GRCh38), rs1024611 associated with higher CCL2 in dendritic cells, and rs1127354 with higher ITPA in CD14+ monocytes. scRNA-seq showed higher CCL2 in Non-effective patients (p<0.001), predominantly across M0/M1/M2 monocytes. ITPA was higher in Effective patients (p=0.018), most notably in M2 monocytes (p<0.001), with elevated ITPA also observed in M1 monocytes of Non-effective patients (p 0.004).
CONCLUSIONS:
Our data prioritise CCL2 and ITPA as candidate pharmacogenetic signals for JAKi response. Given the use of a persistence-based effectiveness endpoint and the exploratory nature of secondary EULAR-based outcome assessments, independent replication using standardised ACR/EULAR outcomes is warranted.
